Project Summary There is an increasing interest in the use of non-invasive electromagnetic stimulation for therapeutic interventions as well as understanding of the functioning of the healthy human brain. Most of the tradi- tional protocols involve stimulation of a single target/focus region. However, evidence is mounting that a wide range of neuronal processing tasks rely on large-scale networks and their synchronization, sug- gesting that multi-focal stimulation would be a particularly promising avenue for enhanced neuromodu- lation protocols. Measuring the response of the brain networks to the stimulation is needed to quantify the effects and therefore concurrent brain mapping methodologies are necessary. To this end, both EEG and fMRI have been employed previously. We consider that the key to maximizing the potential of multi-focal scanning stimulation is the integration of the stimulation and imaging recording as it enables on-line analysis of the brain responses and also allows closed-loop paradigms to be developed. In this TRD, we leverage on our unique expertise in electromagnetic brain stimulation, imaging, and computa- tional modeling to provide a set of tools for the scientific community to promote the integration and ap- plication of multifocal brain imaging and stimulation. Naturally, the single-channel stimulation system users will benefit from the developed methods as well. In Aim 1, we will optimize the anatomical and functional MRI acquisition protocols to enable employing our recently published fast and accurate TMS- induced electric field (E-field) modeling approach to be adopted to computational targeting. In Aim 2, we will develop software (MNE-TMS), with an interface between the stimulation and recording devices that enable real-time analysis of the induced activations using our MNE-CPP platform and control of the stimulating devices. In Aim 3, we will incorporate the geometrical relationships of the neuronal ele- ments with respect to the stimulating E-fields need to be determined to understand the activations at mesoscopic and microscopic levels. In particular, we will extend our previously published methods to allow accurate reconstructions of the white matter bundles as they exit/enter the cortical mantle with of 1 mm resolution in vivo. We will couple the cortical surface geometry reconstructions to simulate the effects of the E-field on various neuronal elements that will allow us predicting the likelihood of the stimulus to engage different activation mechanisms/pathways.